IP Library › Patent Application 18592425
Patent Application
App. No. 18/592,425

ANTI-PD-L1 AND IL-2 CYTOKINES

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Patent No.
US None
App. No.
18/592,425
Abstract

The present invention relates to anti-PD-L1 antibodies, bispecific antibodies containing one domain with specificity to PD-L1, and to immunocytokines comprising an anti-PD-L1 antibody fused to a cytokine, such as IL-2. The present invention also provides methods of treatment, uses and pharmaceutical compositions comprising the antibodies, bispecific antibodies and immunocytokines.

Claims (53)

1 . An immunocytokine comprising an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the heavy chain comprises in N- to C-terminal direction:

a) a V H domain comprising CDRH1, CDRH2 and CDRH3; and

b) a heavy chain constant region;

and wherein the light chain comprises in N- to C-terminal direction:

c) a V L domain comprising CDRL1, CDRL2 and CDRL3;

d) a light chain constant region, (C L ); and

wherein one of the heavy chain or the light chain further comprises in N- to C-terminal direction

e) an optional linker, (L); and

f) an IL-2 cytokine;

wherein the V H domain and V L domain are comprised by an antigen-binding site that

blocks or inhibits PD-1 binding to PD-L1.

2 - 64 . (canceled)

65 . The immunocytokine of claim 1 ,

wherein the light chain comprises in N- to C-terminal direction:

a) the V L domain comprising CDRL1, CDRL2 and CDRL3;

b) the light chain constant region, (C L );

c) a linker, (L); and

d) the IL-2 cytokine;

wherein the V L domain comprises

i) the CDRL1 sequence of SEQ ID NO: 17 or 20;

ii) the CDRL2 sequence of SEQ ID NO: 18 or 21;

iii) the CDRL3 sequence of SEQ ID NO: 19 or 22; and

wherein the V H domain comprises

i) the CDRH1 sequence of SEQ ID NO: 7 or 10;

ii) the CDRH2 sequence of SEQ ID NO: 8 or 11;

iii) the CDRH3 sequence of SEQ ID NO: 9 or 12.

66 . The immunocytokine of claim 65 , wherein the V H domain is derived from the recombination of a human IGHV3 V H gene segment, a human D gene segment, and a human IGHJ5 J H gene segment, and wherein the V L domain is derived from the recombination of a human IGκV1D V κ gene segment and a human J κ gene segment.

67 . The immunocytokine of claim 66 , wherein the human V H gene segment is IGHV3-9*01, the human J H gene segment is IGHJ5*02, and the human V κ gene segment is IGKV1D-39*01.

68 . The immunocytokine of claim 65 , wherein the V H domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 13.

69 . The immunocytokine of claim 65 , wherein the V L domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 23.

70 . The immunocytokine of claim 65 , wherein the immunocytokine further comprises a human constant region.

71 . The immunocytokine of claim 70 , wherein the human constant region is an IgG1 constant region.

72 . The immunocytokine of claim 65 , wherein the V H domain comprises the amino acid sequence of SEQ ID NO: 13 and the V L domain comprises the amino acid sequence of SEQ ID NO: 23.

73 . The immunocytokine of claim 65 , wherein the IL-2 cytokine is human IL-2 (hIL-2) or a variant thereof.

74 . The immunocytokine of claim 73 , wherein the hIL-2 comprises or consists of the amino acid sequence of SEQ ID NO: 301 or a variant thereof comprising a modification at the N-terminus of SEQ ID NO: 301.

75 . A pharmaceutical composition comprising the immunocytokine of claim 1 and a pharmaceutically acceptable excipient, diluent, or carrier.

76 . A kit comprising the pharmaceutical composition of claim 75 and a label or instructions comprising a marketing authorization number.

77 . The immunocytokine of claim 65 , wherein the V H domain comprises the amino acid sequence of SEQ ID NO: 13.

78 . The immunocytokine of claim 65 , wherein the V L domain comprises the amino acid sequence of SEQ ID NO: 23.

79 . The immunocytokine of claim 65 , wherein the V H domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 13, and the V L domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 23.

80 . The immunocytokine of claim 1 , wherein the antigen binding site specifically binds PD-1.

81 . The immunocytokine of claim 1 , wherein the antigen binding site specifically binds PD-L1.

82 . A method of treating a PD-L1-mediated disease or condition in a human subject, the method comprising administering to the human subject a therapeutically effective amount of an immunocytokine, wherein the immunocytokine comprises an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the heavy chain comprises in N- to C-terminal direction:

a) a V H domain comprising CDRH1, CDRH2 and CDRH3; and

b) a heavy chain constant region;

and wherein the light chain comprises in N- to C-terminal direction:

c) a V L domain comprising CDRL1, CDRL2 and CDRL3;

d) a light chain constant region, (C L ); and

wherein one of the heavy chain or the light chain further comprises in N- to C-terminal direction

e) an optional linker, (L); and

f) an IL-2 cytokine;

wherein the V H domain and V L domain are comprised by an antigen-binding site that blocks or inhibits PD-1 binding to PD-L1.

83 . A nucleic acid that encodes a heavy chain and/or a light chain of the immunocytokine of claim 1 .